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Gaining Insight Into Blood Stem Cell Generation

A recent study has illuminated the importance of a cellular protein called GATA2 in the generation and survival of blood (hematopoietic) stem cells in mice. Hematopoietic stem cells (HSCs) give rise to all the types of blood cells, including red blood cells, but the molecular mechanisms regulating the generative process are not completely understood. In contrast to HSCs, hematopoietic progenitor cells (HPCs) are relatively immature cells that are precursors to a fully mature (differentiated) cell of the same tissue type but that have only a limited capacity to differentiate into more than one cell type as HSCs do. As cells and tissues develop in the embryo, the process by which they take on specific characteristics involves cellular proteins called transcription factors, which regulate whether genes are turned on or off. Consistent with a potential role in HSC generation, the transcription factor GATA2 is known to be present in cells implicated in the formation of hematopoietic tissue in the developing mouse embryo, but its function in the generation of HSCs is unknown.

Using a “conditional knockout” strategy, investigators sought to examine what, if any, role GATA2 plays in HSC generation. Through this genetic engineering approach, scientists can produce mice that lack a specific gene only under certain conditions—a so-called conditional knockout. This approach contributes valuable information about the normal function of a gene and its encoded product, such as GATA2, by allowing scientists to observe the consequences of its absence at specific times or developmental stages, and/or in particular tissues. The collective findings from this study indicate that GATA2 is required for HSC generation and HPC formation during embryonic development. In addition, GATA2 is required for survival of HSCs and HPCs in the developing embryo. Thus, these results highlight a unique role for GATA2 function in mouse embryonic hematopoiesis and should inform future regenerative approaches designed to treat blood diseases.